DESCRIPTION: This is a competitive renewal to examine the biochemical and molecular determinants of variation in HIV. The experiments are organized into four specific aims. The first aim is to characterize mutations that arise in natural viral sequences rather than indicator sequences. The second is to determine whether vif, vpr, and nef affect mutation rate. The third is to assess the contribution of RT fidelity to mutation rate. The last aim is to determine the contribution of RNA pol II to mutation.